Biochemical prediction of response of bone metastases to treatment.

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment

A qualitative study of primary care clinicians' views of treating childhood obesity

Background: The prevalence of childhood obesity is rising and the UK Government have stated a commitment to addressing obesity in general. One method has been to include indicators relating to obesity within the GP pay-for-performance Quality and Outcomes Framework (QOF) contract. This study aimed to explore general practitioners' and practice nurses' views in relation to their role in treating childhood obesity. Methods: We interviewed eighteen practitioners (twelve GPs and six nurses) who worked in general practices contracting with Rotherham Primary Care Trust. Interviews were face to face and semi structured. The transcribed data were analysed using framework analysis. Results: GPs and practice nurses felt that their role was to raise the issue of a child's weight, but that ultimately obesity was a social and family problem. Time constraint, lack of training and lack of resources were identified as important barriers to addressing childhood obesity. There was concern that the clinician-patient relationship could be adversely affected by discussing what was often seen as a sensitive topic. GPs and practice nurses felt ill-equipped to tackle childhood obesity given the lack of evidence for effective interventions, and were sceptical that providing diet and exercise advice would have any impact upon a child's weight. Conclusion: GPs and practice nurses felt that their role in obesity management was centred upon raising the issue of a child's weight, and providing basic diet and exercise advice. Clinicians may find it difficult to make a significant impact on childhood obesity while the evidence base for effective management remains poor. Until the lack of effective interventions is addressed, implementing additional targets (for example through the QOF) may not be effective

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Permeating the social justice ideals of equality and equity within the context of Early Years: challenges for leadership in multi-cultural and mono-cultural primary schools

The ideology and commitment of social justice principles is central to Early Years practice, however, the term social justice in education is complex and remains contested. This paper explores the ideology of social justice through links between equality and equity and how it is embedded within Early Years, and what remain the potential challenges for leadership. Interviews in English multi-cultural and mono-cultural primary schools were conducted. Findings showed that the ideology of social justice, equality and equity was interpreted differently. Multi-cultural schools appear to use a greater variety of activities to embed social justice principles that involved their diverse communities more to enrich the curriculum. In mono-cultural schools leadership had to be more creative in promoting equality and equity given the smaller proportion of their diverse pupil and staff population. Tentative conclusions suggest that the vision for permeating equality and equity in Early Years, at best, is at early stages

Secondary school pupils' preferences for different types of structured grouping practices

The aim of this paper is to explore pupils’ preferences for particular types of grouping practices an area neglected in earlier research focusing on the personal and social outcomes of ability grouping. The sample comprised over 5,000 year 9 pupils (aged 13-14 years) in 45 mixed secondary comprehensive schools in England. The schools represented three levels of ability grouping in the lower school (years 7 to 9). Pupils responded to a questionnaire which explored the types of grouping that they preferred and the reasons for their choices. The majority of pupils preferred setting, although this was mediated by their set placement, type of school, socio-economic status and gender. The key reason given for this preference was that it enabled work to be matched to learning needs. The paper considers whether there are other ways of achieving this avoiding the negative social and personal outcomes of setting for some pupils

Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids

Background: Many Gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. Methodology/Results: Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable a-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. Conclusion: Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and othe

Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR

The role of the General Practitioner in weight management in primary care – a cross sectional study in General Practice

BACKGROUND: Obesity has become a global pandemic, considered the sixth leading cause of mortality by the WHO. As gatekeepers to the health system, General Practitioners are placed in an ideal position to manage obesity. Yet, very few consultations address weight management. This study aims to explore reasons why patients attending General Practice appointments are not engaging with their General Practitioner (GP) for weight management and their perception of the role of the GP in managing their weight. METHODS: In February 2006, 367 participants aged between 17 and 64 were recruited from three General Practices in Melbourne to complete a waiting room self - administered questionnaire. Questions included basic demographics, the role of the GP in weight management, the likelihood of bringing up weight management with their GP and reasons why they would not, and their nominated ideal person to consult for weight management. Physical measurements to determine weight status were then completed. The statistical methods included means and standard deviations to summarise continuous variables such as weight and height. Sub groups of weight and questionnaire answers were analysed using the chi2 test of significant differences taking p as < 0.05. RESULTS: The population sample had similar obesity co-morbidity rates to the National Heart Foundation data. 74% of patients were not likely to bring up weight management when they visit their GP. Negative reasons were time limitation on both the patient's and doctor's part and the doctor lacking experience. The GP was the least likely person to tell a patient to lose weight after partner, family and friends. Of the 14% that had been told by their GP to lose weight, 90% had cardiovascular obesity related co-morbidities. GPs (15%) were 4th in the list of ideal persons to manage weight after personal trainer CONCLUSION: Patients do not have confidence in their GPs for weight management, preferring other health professionals who may lack evidence based training. Concurrently, GPs target only those with obesity related co-morbidities. Further studies evaluating GPs' opinions about weight management, effective strategies that can be implemented in primary care and the co-ordination of the team approach need to be done

Assessing the diagnostic accuracy of the identification of hyperkinetic disorders following the introduction of government guidelines in England

<p>Abstract</p> <p>Background</p> <p>Previous studies have suggested that both underdiagnosis and overdiagnosis routinely occur in ADHD and hyperkinesis (hyperkinetic disorders). England has introduced governmental guidelines for these disorders' detection and treatment, but there has been no study on clinical diagnostic accuracy under such a regime.</p> <p>Methods</p> <p>All open cases in three Child and Adolescent Mental Health Services (CAMHS) in the South East of England were assessed for accuracy in the detection of hyperkinetic disorders, using a two-stage process employing the Strengths and Difficulties Questionnaire (SDQ) for screening, with the cut-off between "unlikely" and "possible" as the threshold for identification, and the Development And Well-Being Assessment (DAWBA) as a valid and reliable standard.</p> <p>Results</p> <p>502 cases were collected. Their mean age 11 years (std dev 3 y); 59% were clinically diagnosed as having a hyperkinetic disorder including ADHD. Clinicians had missed two diagnoses of hyperkinesis and six of ADHD. The only 'false positive' case was one that had become asymptomatic on appropriate treatment.</p> <p>Conclusion</p> <p>The identification of children with hyperkinetic disorders by three ordinary English CAMHS teams appears now to be generally consistent with that of a validated, standardised assessment. It seems likely that this reflects the impact of Governmental guidelines, which could therefore be an appropriate tool to ensure consistent accurate diagnosis internationally.</p

Increasing the satisfaction of general practitioners with continuing medical education programs: A method for quality improvement through increasing teacher-learner interaction

BACKGROUND: Continuing medical education (CME) for general practitioners relies on specialist-based teaching methods in many settings. Formal lectures by specialists may not meet the learning needs of practitioners and may cause dissatisfaction with traditional CME. Increasing learner involvement in teaching programs may improve learner satisfaction. METHODS: A quality improvement program for CME for 18 general practitioners in the Tel Aviv region was designed as a result of dissatisfaction with traditional CME activities. A two-step strategy for change was developed. The CME participants first selected the study topics relevant to them from a needs assessment and prepared background material on the topics. In the second step, specialist teachers were invited to answer questions arising from the preparation of selected topics. Satisfaction with the traditional lecture program and the new participatory program were assessed by a questionnaire. The quality criteria included the relevance, importance and applicability of the CME topic chosen to the participant's practice, the clarity of the presentation and the effective use of teaching aids by the lecturer and the potential of the lecturer to serve as a consultant to the participant. RESULTS: The participatory model of CME significantly increased satisfaction with relevance, applicability and interest in CME topics compared to the traditional lecture format. CONCLUSIONS: Increased learner participation in the selection and preparation of CME topics, and increased interaction between CME teachers and learners results in increased satisfaction with teaching programs. Future study of the effect of this model on physician performance is required